tbuckley/cabot-search huggingface dataset:
Abstract 12059: Speckle-Tracking Echocardiography Derived Global Circumferential Strain Predicts Adverse Outcomes in Cardiac Sarcoidosis With Preserved Ejection Fraction
Authors: Joseph Okafor, Alessia Azzu, Raheel Ahmed, Rui Shi, Shreya Ohri, Rakesh Sharma, Kshama Wechalekar, Athol U Wells, A J Baksi, Dudley J Pennell, Vasilis Kouranos, Rajdeep S Khattar
Journal: Circulation (2022)

Introduction: Risk stratification in cardiac sarcoidosis (CS) remains challenging, especially in those with preserved left ventricular ejection fraction (LVEF). Myocardial strain parameters are more sensitive than LVEF for detecting early sub-clinical myocardial dysfunction, but their prognostic value in CS is not known. Methods: We investigated consecutive newly diagnosed CS patients between 2015 and 2018. All patients underwent 2D echocardiography including global longitudinal strain (GLS) and global circumferential strain (GCS) measurement, cardiac magnetic resonance (CMR) for late gadolinium enhancement (LGE) and FDG-PET imaging to derive the maximum standard uptake value (SUVmax). The LGE score was quantified as the number of myocardial segments with LGE. Major adverse cardiac events (MACE) were all-cause death, sustained ventricular arrhythmia (VA), device implantation and new onset heart failure (HF) admission. Results: A total of 120 patients were included with age of 55±12 years; 87% were Caucasian, 43% had hypertension and 13% had diabetes. Mean LVEF was 55±12.3%, GLS was -13.4±4.2%, GCS was -16.0±5.6% and regional wall motion abnormalities (RWMA) occurred in 36% of cases. During median follow-up of 4.3 years, 43 patients experienced MACE consisting of 15 deaths, 19 VAs, 7 devices and 2 HF admissions. In multivariate analysis syncope, ethnicity, echo-derived left atrial volume and RWMA were independent predictors of MACE along with CMR-derived right ventricular EF and LGE score. Although GLS and GCS were lower in those with MACE, neither had independent prognostic value. SUVmax was also not predictive of events. In a subgroup analysis of the 86 patients with LVEF ≥50%, 20 patients experienced MACE. Multivariate analysis showed non-Caucasian ethnicity (HR 3.18 [95% CI 1.02-9.88]; P = 0.04), RWMA (HR 3.76 [95% CI 1.29-10.98]; P = 0.02), LGE-score (HR 1.26 95% CI 1.05-1.51]; P = 0.01 and GCS (HR 1.18 [95% CI 1.04-1.36]; P = 0.01) were independent predictors of MACE. A GCS value above the optimal cut-off of -16.4% was associated with a worse outcome (log-rank P = 0.005). Conclusion Ethnicity, RWMA and LGE-score are robust markers of outcome in newly diagnosed CS. Reduced GCS provides additional prognostic information in those with preserved LVEF.
Abstract 11076: Visualization of Cardiac Uptake of Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles After Intramyocardial or Intravenous Injection in Murine Myocardial Infarction
Authors: Cynthia M Xu, Sharif A Sabe, Mohamed Sabra, Frank W Sellke, Ruhul Abid
Journal: Circulation (2022)

Introduction: In animal models, human bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EV) have been found to have beneficial effects in cardiovascular disease, but only when administered via intramyocardial injection. The biodistribution of either intravenous or intramyocardial injection of MSC-EV in the presence of myocardial injury is uncharacterized at this time. Hypothesis: Intramyocardial injection will ensure delivery of MSC-EV to the ischemic myocardium, while intravenous injection will not. Methods: Human bone marrow mesenchymal stem cells were cultured, and MSC-EV were isolated and characterized. The MSC-EVs were then labeled with DiD lipid dye. FVB mice with normal cardiac function underwent left coronary artery ligation followed by either peri-infarct intramyocardial or tail vein injection of 3*10 6 or 2*10 9 particles of DiD-labeled MSC-EV or a DiD-saline control. The heart, lungs, liver, spleen and kidneys were harvested 2 hours post-injection and were submitted for fluorescent molecular tomography imaging. Results: Myocardial uptake of MSC-EV was only visualized after intramyocardial injection of 2*10 9 particles (p = 0.029), and was not detected after tail vein injection of MSC-EV (Figure 1). There were no significantly detectable MSC-EV uptake in other organs after intramyocardial injection, though there was possible focal lung uptake. After tail vein injection of MSC-EV, liver (p = 0.048) and spleen (p = 0.048) appeared to have diffuse MSC-EV uptake. Conclusions: Even in the presence of myocardial injury, only intramyocardial but not intravenous administration resulted in detectable levels of MSC-EV in the ischemic myocardium. This study confirms the role for intramyocardial injection in maximal and effective delivery of MSC-EV. Our ongoing studies aimed at developing bioengineered MSC-EV for targeted delivery to the heart may make MSC-EV clinically applicable.
Abstract 11710: Sex Differences in Right Ventricular Flow Dynamics and Kinetic Energy in Healthy Volunteers
Authors: XIAODAN ZHAO, Shuang Leng, Ru-San Tan, Ping Chai, Jennifer A Bryant, Lynette Teo, Marielle V Fortier, Ching Ching Ong, Ting Ting Low, Angela Koh, Shuo Zhang, Rob J van der Geest, Teng Hong Tan, James Wei Luen Yip, Ju Le Tan, Liang Zhong
Journal: Circulation (2022)

Introduction: Accurate right ventricular (RV) flow and function is crucial for optimal cardiovascular health. However, research on RV flow and function has lagged behind that for the left ventricle. Whole-heart 4D flow cardiovascular magnetic resonance (CMR) uniquely quantifies simultaneous multi-directional phasic blood flow and kinetic energy (KE). Gender differences in these parameters have not been well studied and may contribute to the predilection for developing certain cardiovascular diseases among females. This study aims to compare RV flow and KE parameters in healthy female and male subjects. Methods: Healthy subjects from 2 centers (n=163) were prospectively recruited to undergo 4D flow CMR. RV flow components —direct flow, retained inflow, delayed ejection flow and residual volume —and KE (KE=1/2·ρ blood · V voxel · v 2 where ρ blood is blood density 1.06 g/cm 3 ; V voxel , voxel volume; and v , velocity) were calculated. All KE parameters were indexed to RV end-diastolic volume (KEi EDV ) and expressed in μJ/ml. KEi EDV parameters at physiologically relevant epochs (global [entire cycle], systole, diastole) and cardiac cycle time points (peak systole, peak E-wave, peak A-wave) were extracted from a time-resolved KEi EDV curve. Results: Compared to males (n=95, mean age 44 years old), females (n=68, mean age 42 years old) had higher RV ejection fraction but smaller RV volumes; higher RV direct flow (38 vs 34%, P=0.007) and delayed ejection flow (17 vs 15%, P=0.043) and lower RV residual volume (27 vs 33%, P=0.001). Females had higher global KEi EDV (8.9 vs 7.5μJ/ml, P=0.005), diastolic KEi EDV (6.7 vs 5.6μJ/ml, P&lt;0.001), peak E-wave KEi EDV (14.4 vs 11.9μJ/ml, P&lt;0.001) and E-wave/A-wave ratio (1.68 vs 1.30, P=0.028) than males. No differences were observed for RV retained inflow, RV peak systolic, average systolic and peak A-wave KEi EDV between gender. Conclusion: Females have higher RV direct flow and lower RV residual volume, higher preload-adjusted RV global, average diastolic, peak E-wave and E-wave/A-wave ratio KEi EDV , compared to males by 4D flow cardiovascular magnetic resonance imaging. These parameters that related to right heart efficiency may lead to further understanding of the sex-based predispositions to right heart disease.
Abstract 12482: Practical Adherence to AHA/ACC 2018 Guidelines Among Secondary Prevention Patients
Authors: Aleesha Kainat, Yousef Alish, Mohammad Ateya, Michael J Becich, Alison Bradley, David A Demicco, Soledad Fernandez, Dan Ford, Rozelle Hegeman-Dingle, Wenke Hwang, Jong Jeong, Martha O Jurczak, H Lester Kirchner, Euan McLeod, Kathleen M McTigue, Richard S Morgan, Anuradha Paranjape, Phillip Saccone, Neena Thomas, Kevin A Townsend, David A Williams, Jonathan Arnold
Journal: Circulation (2022)

Introduction: Patients with ASCVD are at increased risk for CV events. The 2018 AHA/ACC lipid guidelines recommend treating these patients with high intensity or maximally tolerated statin therapy. The objective of this study was to describe lipid lowering treatment (LLT) patterns and lipid values across 7 regional health systems. Methods: We conducted a cross-sectional analysis of electronic health records transformed into the PCORnet common data model (CDM) from 7 sites in the PaTH Clinical Research Network. Adults were eligible for inclusion if an LDL-C value was measured within the past year and &gt; 6 months of pre-index data were available prior to the first LDL-C value in the study period. We defined computable phenotypes for adults meeting AHA/ACC criteria for ASCVD at very high risk (VHR) and not at very high risk (NVHR). Medication use was assessed during the study period using the CDM prescribing table. Descriptive statistics were used to summarize LLT and lipid values within these groups and across sites. Results: NVHR patients (n=69,854) had mean (SD) LDL-C, TG and non-HDL-C of 92.1 (37), 138 (104) and 114.4 (43) mg/dl, respectively; 71% had LDL-C &gt; 70 mg/dL, 30% had TGs 150-500 mg/dL, and 61% had non-HDL-C ≥ 100 mg/dL. VHR patients (n=117, 689) had mean (SD) LDL-C, TG and non-HDL-C of 82.9 (43), 138.5 (99), and 106 (43) mg/dl, respectively; 58.6% had LDL-C &gt; 70 mg/dL, 30.5% had TGs 150-500 mg/dL, and 49.8% had non-HDL-C ≥ 100 mg/dL. Documented LLT in NVHR and VHR patients was 58% and 69% for statin therapy, 25% and 36% for high intensity statin therapy, 12% and 16% for statin therapy + another LLT, while 37% and 27% had no documented LLT. Conclusions: In this cross-sectional study of NVHR and VHR ASCVD patients, although most had documented statin therapy, only 25% and 36%, respectively were on high intensity statins while more than a quarter of patients had no documented LLT. Recorded LDL, TG and non-HDL-C lab values suggest there may be unaddressed risk in these populations.
Abstract 119: Resuscitation Outcomes In Covid-19-associated Out-of-hospital Cardiac Arrest
Authors: Kellen Albrecht, Jason Bartos, Andrea M Elliott
Journal: Circulation (2022)

BACKGROUND: Since the beginning of the pandemic, there have been numerous reports of increased mortality in the setting of both in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) in patients with novel coronavirus-19 (COVID-19) infection. Due to these alarming mortality rates, it has been proposed that resuscitation may represent futility when COVID-19 is suspected or confirmed in patients with cardiac arrest. However, it continues to remain unclear whether the currently available data is sufficient to be broadly applied to all patients and hospitals. HYPOTHESIS: In COVID-positive patients presenting after OHCA, resuscitation should be pursued and is not futile as has previously been suggested. METHODS: 264 consecutive patients presenting to the University of Minnesota Medical Center were obtained from the Cardiac Arrest Registry to Enhance Survival (CARES) database from March 2020 through April 2022. Patient data was obtained retrospectively for COVID19 infection status, initial documented arrest rhythm, and survival to hospital discharge. RESULTS: 264 patients were collected for analysis with 2 being excluded due to incomplete data. Of the remaining 262, 16 were found to be COVID-positive. Of these patients, 2 (12.5%) survived to hospital discharge compared to 72 (29.2%) in the group without COVID. In COVID-positive patients presenting with initially shockable rhythm (11 patients), survival was 18.2% compared with no survival noted in those with initially non-shockable rhythm. 9 patients with COVID were cannulated for ECMO, with 1 (11.1%) surviving to hospital discharge. CONCLUSIONS: This study provides insight into resuscitation in the setting of OHCA when COVID is suspected or confirmed. Though small in overall number of patients, our study indicates that resuscitation efforts in COVID-positive patients are not futile, as has previously been suggested.
Abstract 11302: Natural Heart Regeneration After Myocardial Infarction in Newborn Rats Provides Ultra-Long-Term Protection From Cardiac Dysfunction and Mortality
Authors: Hanjay Wang, Hye Sook Shin, Danielle Mullis, Nicholas Tran, Jinsuh Jung, Matthew Wu, Stefan Elde, Yuanjia Zhu, Y. Joseph J Woo
Journal: Circulation (2022)

Introduction: Newborn rats exhibit natural heart regeneration after myocardial infarction (MI), yielding no evidence of cardiac dysfunction or scar at 3 weeks post-MI. This phenotype is absent when MI occurs after 1 week of age. The long-term function of the regenerated heart and its impact on survival post-MI have not been studied. We hypothesized that natural heart regeneration preserves cardiac function and normalizes survival through adulthood. Methods: Wistar rat neonates (n=51) underwent left anterior descending coronary artery ligation on postnatal day 1 (P1, n=17) or postnatal day 9 (P9, n=12). Sham surgery was performed in littermates (P1 n=12, P9 n=10). The rats were observed for the entirety of their lifespan, reaching 18 months post-MI (equivalent to 45 human years) at the time of this analysis. Echocardiography was obtained at 15 months post-MI. After each mortality event, hearts were sectioned and stained with Masson’s trichome. Results: Echocardiography at 15 months after P1 MI vs P1 sham surgery revealed no differences in left ventricular (LV) wall thickness (p=0.881, Fig 1A) or end-diastolic diameter (p=0.118, Fig 1B), and LV ejection fraction (EF) was sustained within normal limits (63.2% vs 68.5%, p=0.003, Fig 1C). In contrast, after P9 MI, severe LV wall thinning (p&lt;0.001), massive LV dilation (p&lt;0.001), and profoundly depressed EF were observed (41.8% vs 69.1%, p&lt;0.001). Concordant results were observed for both sexes. Trace scar was detected after P1 MI, while large infarcts and LV aneurysms were observed after P9 MI (Fig 1D). At 18 months post-MI, overall survival was 13/17 (76.5%) in the P1 MI group compared to 9/12 (75.0%) in the P1 sham group (p&gt;0.999) and 3/12 (25.0%) in the P9 MI group (p=0.009). Conclusions: Natural heart regeneration mechanisms may offer long-term protection from LV dysfunction and mortality after cardiac injury, suggesting potential applications in congenital heart surgery and as a durable treatment for ischemic cardiomyopathy.
Abstract 12118: Social Disadvantage, Coronary Artery Calcium, and Their Interplay, in the Prediction of Atherosclerotic Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis
Authors: Isaac Acquah, Miguel Cainzos Achirica, Mohamad Taha, Sadeer Al-Kindi, Safi U Khan, Garima Sharma, Michael J Blaha, Matthew Budoff, Khurram Nasir
Journal: Circulation (2022)

Introduction: Social determinants of health (SDOH) are key for the identification of populations at increased risk of developing cardiovascular risk factors (RFs) and ASCVD. In contrast, whether at the individual level SDOH improve current ASCVD risk prediction paradigms beyond traditional RFs and CAC, is unknown. Also, while CAC predicts outcomes across a wide range of risk profiles, its performance across groups with increasing levels of social vulnerability has not been evaluated. Methods: MESA is a prospective study of US adults free of clinical ASCVD at baseline. We developed an SDOH index inclusive of 14 determinants from 5 domains. The index ranged 0-1 and was divided into quartiles, with higher ones representing worse SDOH. Cox regression was used to evaluate the adjusted associations between CAC, SDOH, their interplay, and ASCVD events; and C-statistics were used to assess improvement in risk discrimination for prediction of all/hard events with CAC, SDOH, and both. Results: We included 6,479 MESA participants (50% with CAC=0, 24% CAC&gt;100). The incidence of hard ASCVD events was higher for increasing CAC scores across all SDOH quartiles ( Figure Panel A ). The lowest incidence was noted in those with CAC=0 and favorable SDOH (2/1000 person-ys) and highest in those with CAC&gt;100 and most unfavorable SDOH (20.6/1000 person-ys). CAC improved the discriminatory ability of prediction models, while improvements with SDOH were smaller and were none on top of CAC ( Panel B ). Results were consistent in analyses that evaluated education and income as SDOH exposures. Conclusion: CAC stratifies ASCVD risk across the spectrum of social vulnerability and can guide personalized risk management also among most socially vulnerable populations. In contrast, SDOH fail to improve risk prediction beyond traditional RFs and CAC. Our results provide further support to current ASCVD risk assessment paradigms in the US, and suggest that SDOH have a limited role in this specific setting.
Abstract 12072: EKG Appearance and Evolution of Baseline EKG-Characteristics in the Worldwide First Genetically Modified Porcine-to-Human Xenotransplant (“Pig Heart-in-Human Body”)
Authors: Calvin Kagan, Richard S Amara, Muhammad Haq, Muhammad Mohiuddin, Susie N Hong-Zohlman, Manjula Ananthram, Charles C Hong, Vincent Y See, Stephen Shorofsky, Bartley Griffith, Timm Dickfeld
Journal: Circulation (2022)

Introduction: The worldwide first genetically modified porcine-to-human cardiac xenotransplantation was performed in January 2022 at the University of Maryland with the recipient surviving for 61 days. Methods: Daily 12- lead ECGs were obtained during the post-operative period. Results: Accepted “pig heart-in-pig body” ECG parameters demonstrate a short PR interval (50-120ms), short QRS (70-90ms) and short QT (260-380ms). However, the first-ever EKG of a genetically modified heart xenotransplant (“pig heart-in-human body”) demonstrated a relatively longer PR interval of 190ms, QRS duration of 138ms and QT of 538ms (in setting of sinus bradycardia, interventricular conduction delay and inferior/antero-lateral T wave inversions; Figure 1). Prolonged intrinsic PR intervals remained stable during the post-operative course with 210±22ms [range 142-246ms]. However, atrial pacing demonstrated evidence of decremental intra-atrial conduction delay/AV-conduction delay most pronounced on day 12 (PR: 380ms). QRS duration remained prolonged with 145±16ms [range 116-192ms] but shortened during the post-operative course (day 21-40 vs 41-60: 148±14ms vs 132±11ms; p&lt;0.001). Increased QT persisted with 509±54ms [range 384-650ms] with dynamic fluctuations (QT nadir around day 14 (428±22ms vs 533±36ms; p&lt;0.001). Conclusions: ECG parameters of the first genetically modified porcine-to-human cardiac xenotransplant (“pig heart-in-human body”) demonstrated prolongation over the usually encountered ECG measurements in the donor (“pig heart- in-pig body”) including changes in cardiac depolarization and repolarization. Prolonged ECG parameters persisted but showed dynamic changes during post-operative period. This provides a first insight into the novel and evolving field of xenotransplanation suggesting a complex interplay of inter-species physiology and porcine denervation in addition to post-surgical and medication-related changes.
Abstract 12476: Dapagliflozin versus Empagliflozin and the Risk for Cardiovascular Outcomes in Patients With Type 2 Diabetes: A Nationwide Population-Based Study
Authors: Jaehyun Lim, Bongseong Kim, You-Jung Choi, Hyun-Jung Lee, Kyung-Do Han, Heesun Lee, Jun-bean Park, Hyung-kwan Kim, Yong-Jin Kim
Journal: Circulation (2022)

Introduction: Dapagliflozin and empagliflozin are the two most widely used sodium-glucose co-transporter 2 inhibitors (SGLT2i) for type 2 diabetes (T2DM) worldwide. The study was conducted to compare the cardiovascular outcomes of two SGLT2i, dapagliflozin and empagliflozin. Methods: We conducted a nationwide cohort study using the Korean National Health Insurance Service database and an active-comparator new-user design. Patients newly prescribed either dapagliflozin or empagliflozin between 2016 and 2018 for T2DM were retrospectively analyzed and matched in a 1:1 ratio based on propensity scores estimated using 53 potential confounding variables. The primary outcome was major adverse cardiovascular events (MACE), which is a composite of myocardial infarction, ischemic stroke, heart failure (HF) events (i.e., hospitalization for HF or HF-related death), and cardiovascular death. Secondary outcomes were HF events, cardiovascular death, and all-cause mortality. Results: A total of 145,502 patients were included in the final analysis (mean age 57±12 years, 57% male). During mean follow-up of 2.1±0.7 years, there was no significant difference in the incidence of MACE between the two groups (incidence rate 6.95 vs. 7.33 per 1000 person-years). The hazard ratio [HR] for dapagliflozin to empagliflozin users was 0.95 (95% confidence interval [CI] 0.87-1.03; P= 0.199). Regarding secondary outcomes, however, compared with empagliflozin users, dapagliflozin users had a lower risk of HF events (HR 0.84, 95% CI 0.71-0.98; P= 0.032), and cardiovascular death (HR 0.82, 95% CI 0.68-1.00; P= 0.047), other than all-cause mortality (HR 1.00, 95% CI 0.92-1.09; P= 0.934). Conclusions: In this large nationwide cohort study, the risk of MACE was similar between dapagliflozin and empagliflozin users. Yet, dapagliflozin users, as compared with empagliflozin users, were associated with a reduced risk of hospitalization for HF or HF-related death and cardiovascular death.
Abstract 12459: Hemodynamic Progression of Mitral Annular Calcification: Prevalence, Characteristics, and Clinical Implications
Authors: Hee Jeong Lee, Kyungeun Ha, Seo-Yeon Gwak, Kyu Kim, Kyu-Yong Ko, Iksung Cho, Geu-Ru Hong, Jong-Won Ha, Chi Y Shim
Journal: Circulation (2022)

Background: A recent study demonstrated that transmitral mean diastolic pressure gradient (MDPG) in patients with mitral annular calcification (MAC) is associated with increased mortality, however, the longitudinal hemodynamic progression over time in patients with MAC and its characteristics are unclear. In this study, the clinical and echocardiographic characteristics of MAC correlated with hemodynamic progression and its clinical implications were investigated. Methods: In total, 161 patients (mean age 74.7±10.5 yeas, 63 men) with MAC were identified by index transthoracic echocardiography (TTE) between January 2012 and June 2016 and performed follow-up TTE after 3 years. Stable MAC (n=146, 90.7%) was defined as a difference of transmitral mean pressure gradient (MDPG) less than 2 mmHg between initial and follow-up TTE, and progressive MAC (n=15. 9.5%) was defined as MDPG increased above 2mmHg. Results: There was no significant difference of baseline characteristics between the group with stable MAC and progressive MAC. In the group of progressive MAC compared to that of stable MAC, a proportion of moderate-to-severe MAC (66.7 vs. 28.1%, p =0.002), significant MS (26.7 vs. 8.2%, p =0.046), maximal thickness of MAC (0.7±0.5 vs. 0.5±0.3, p =0.023), and MDPG (2.8±1.7 vs. 2.2±1.5, p =0.048) were significantly higher at the index TTE ( Figure ). In the group with progressive MAC, increase in left atrial (LA) volume index and pulmonary artery systolic pressure were significant. In-5-year mortality and newly developed atrial fibrillation tended to be more common in progressive MAC group, but there was no statistical significance. Conclusions: Hemodynamic progression occurs in about 10% of patients over 3 years. Patients with progressive MAC have larger baseline MAC thickness and calcification extent, even if MDPG is less than 3 mmHg. Patients with progressive MAC are more likely to develop LA enlargement and pulmonary hypertension, which are prone to poor outcome.